Progesterone attenuates astro- and microgliosis and enhances oligodendrocyte differentiation following spinal cord injury

• Published in: Experimental neurology Vol. 231; no. 1; pp. 135 - 146
• Main Authors: Labombarda, Florencia, González, Susana, Lima, Analia, Roig, Paulina, Guennoun, Rachida, Schumacher, Michael, De Nicola, Alejandro F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.09.2011; Elsevier
• Subjects: Animals; Astrocytes; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - physiology; Astrogliosis; Biological and medical sciences; Cell activation; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell proliferation; Demyelination; Differentiation; Disease Models, Animal; Glial cells; Glial fibrillary acidic protein; Glial stem cells; Gliosis; Inflammation; Injuries of the nervous system and the skull. Diseases due to physical agents; Macrophages; Male; Medical sciences; Microglia; Microglia - cytology; Microglia - drug effects; Microglia - physiology; Microgliosis; Myelination; Myelitis - drug therapy; Myelitis - pathology; Neurology; Neuroprotection; Oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - drug effects; Oligodendroglia - physiology; Progesterone; Progesterone - pharmacology; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - pathology; Spinal cord injury; Stem cells; Stem Cells - drug effects; Stem Cells - physiology; Traumas. Diseases due to physical agents; Astrogliosis; Neuroprotection; Microgliosis; Progesterone; Spinal cord injury; Oligodendrocytes; Nervous system diseases; Neuroglia; Ovarian hormone; Oligodendrocyte; Spinal cord trauma; Central nervous system disease; Sex steroid hormone; Spinal cord disease
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2011.06.001

Reactive gliosis, demyelination and proliferation of NG2+ oligodendrocyte precursor cells (OPC) are common responses to spinal cord injury (SCI). We previously reported that short-term progesterone treatment stimulates OPC proliferation whereas chronic treatment enhances OPC differentiation after SCI. Presently, we further studied the proliferation/differentiation of glial cells involved in inflammation and remyelination in male rats with SCI subjected to acute (3 days) or chronic (21 days) progesterone administration. Rats received several pulses of bromodeoyuridine (BrdU) 48 and 72 h post-SCI, and sacrificed 3 or 21 days post-SCI. Double colocalization of BrdU and specific cell markers showed that 3 days of SCI induced a strong proliferation of S100β+ astrocytes, OX-42+ microglia/macrophages and NG2+ cells. At this stage, the intense GFAP+ astrogliosis was BrdU negative. Twenty one days of SCI enhanced maturation of S100β+ cells into GFAP+ astrocytes, but decreased the number of CC1+ oligodendrocytes. Progesterone treatment inhibited astrocyte and microglia /macrophage proliferation and activation in the 3-day SCI group, and inhibited activation in the 21-day SCI group. BrdU/NG2 double labeled cells were increased by progesterone at 3 days, indicating a proliferation stimulus, but decreased them at 21 days. However, progesterone-enhancement of CC1+/BrdU+ oligodendrocyte density, suggest differentiation of OPC into mature oligondendrocytes. We conclude that progesterone effects after SCI involves: a) inhibition of astrocyte proliferation and activation; b) anti-inflammatory effects by preventing microglial activation and proliferation, and c) early proliferation of NG2+ progenitors and late remyelination. Thus, progesterone behaves as a glioactive factor favoring remyelination and inhibiting reactive gliosis. ► Spinal cord injury disturbs the function of glial cell types including astrocytes, oligodendrocytes and microglia. ► In rats with spinal cord injury progesterone treatment inhibits proliferation and activation of astrocytes and microglia. ► Progesterone stimulates proliferation of oligodendrocyte progenitors and induces their differentiation and maturation. ► Thus, progesterone emerges as a glioactive factor favoring remyelination and inhibiting reactive astro and microgliosis.